tbuckley/cabot-search huggingface dataset:
Immune Responses in Controllers of HIV Infection
Authors: Abena K. Kwaa, Joel N. Blankson
Journal: Annual Review of Immunology (2023)

Elite controllers are a heterogeneous group of people living with HIV who control viral replication without antiretroviral therapy. There is substantial evidence that at least some elite controllers are infected with replication-competent virus, thus they may serve as a model of a functional cure of HIV. The mechanisms responsible for virologic control have been actively studied. The most objective data support CD8+ T cell–based mechanisms of control, but other immune responses, mediated by antibodies and natural killer cells, may also play a role in controlling viral replication. In this article, we review the evidence for different mechanisms of immune control in these remarkable individuals.
Precision Approaches to Chronic Obstructive Pulmonary Disease Management
Authors: Matthew Moll, Edwin K. Silverman
Journal: Annual Review of Medicine (2023)

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD heterogeneity has hampered progress in developing pharmacotherapies that affect disease progression. This issue can be addressed by precision medicine approaches, which focus on understanding an individual's disease risk, and tailoring management based on pathobiology, environmental exposures, and psychosocial issues. There is an urgent need to identify COPD patients at high risk for poor outcomes and to understand at a mechanistic level why certain individuals are at high risk. Genetics, omics, and network analytic techniques have started to dissect COPD heterogeneity and identify patients with specific pathobiology. Drug repurposing approaches based on biomarkers of specific inflammatory processes (i.e., type 2 inflammation) are promising. As larger data sets, additional omics, and new analytical approaches become available, there will be enormous opportunities to identify high-risk individuals and treat COPD patients based on their specific pathophysiological derangements. These approaches show great promise for risk stratification, early intervention, drug repurposing, and developing novel therapeutic approaches for COPD.
Generalized pustular psoriasis: A consensus statement from the National Psoriasis Foundation
Authors: April W. Armstrong, Carly A. Elston, Boni E. Elewski, Laura K. Ferris, Alice B. Gottlieb, Mark G. Lebwohl, Cassandra Calabrese, Seemal R. Desai, Kristina C. Duffin, Steven R. Feldman, Dafna D. Gladman, Brad P. Glick, George Han, Jason Harris, Jason E. Hawkes, Sylvia Hsu, Margaret Y. Huang, Robert E. Kalb, Leon H. Kircik, John Koo, G. Michael Lewitt, Wilson J. Liao, Clive Liu, Joseph F. Merola, Ronald B. Prussick, Soumya M. Reddy, Sergio Schwartzman, Jessica N. Smith, Jennifer Soung, Abby S. Van Voorhees, Elizabeth B. Wallace, Jeffrey M. Weinberg, Lara Wine Lee, Paul S. Yamauchi
Journal: Journal of the American Academy of Dermatology (2023)
Polymer‐Initiating Caveolae‐Mediated Endocytosis and GSH‐Responsive MiR‐34a Gene Delivery System for Enhanced Orthotopic Triple Negative Breast Cancer Therapy
Authors: Tian‐Yan Han, Meng‐Lei Huan, Zedong Cai, Wei He, Si‐Yuan Zhou, Bang‐Le Zhang
Journal: Advanced Healthcare Materials (2023)

Gene therapy based on miRNAs has broad application prospects in the treatment of tumors. However, due to degradation and ineffective release during intracellular transport, current gene delivery vectors used for miRNAs limited their actual transfection efficiency. This study develops a novel nonviral vector PEI-SPDP-Man (PSM) that can simultaneously target cellular uptake pathways and intracellular responsive release for miR-34a. PSM is synthesized by connected mannitol (Man) to branched polyethylenimine (PEI) using a disulfide bond. The prepared PSM/miR-34a gene delivery system can induce and enter to tumor cells through caveolae-mediated endocytosis to reduce the degradation of miR-34a in lysosomes. The disulfide bond is sensed at high concentration of glutathione (GSH) in the tumor cells and miR-34a is released, thereby reducing the expression of Bcl-2 and CD44 to suppress the proliferation and invasion of tumor cells. In vitro and in vivo experiments show that through the targeted cellular uptake and the efficient release of miR-34a, an effective antitumor and antimetastasis profiles for the treatment of orthotopic triple negative breast cancer (TNBC) are achieved. This strategy of controlling intracellular transport pathways by targeting cellular uptake pathways in the gene therapy is an approach that could be developed for highly effective cancer therapy.
The respiratory microbiome in childhood asthma
Authors: Gina J. van Beveren, Hager Said, Marlies A. van Houten, Debby Bogaert
Journal: Journal of Allergy and Clinical Immunology (2023)

Asthma is the most prevalent noncommunicable disease in childhood, characterized by reversible airway constriction and inflammation of the lower airways. The respiratory tract consists of the upper and lower airways, which are lined with a diverse community of microbes. The composition and density of the respiratory microbiome differs across the respiratory tract, with microbes adapting to the gradually changing physiology of the environment. Over the past decade, both the upper and lower respiratory microbiomes have been implicated in the etiology and disease course of asthma, as well as in its severity and phenotype. We have reviewed the literature on the role of the respiratory microbiome in asthma, making a careful distinction between the relationship of the microbiome with development of childhood asthma and its relationship with the disease course, while accounting for age and the microbial niches studied. Furthermore, we have assessed the literature regarding the underlying asthma endotypes and the impact of the microbiome on the host immune response. We have identified distinct microbial signatures across the respiratory tract associated with asthma development, stability, and severity. These data suggest that the respiratory microbiome may be important for asthma development and severity and may therefore be a potential target for future microbiome-based preventive and treatment strategies.
Engineered extracellular vesicles efficiently deliver CRISPR-Cas9 ribonucleoprotein (RNP) to inhibit herpes simplex virus1 infection in vitro and in vivo
Authors: Yuanda Wan, Liren Li, Ruilin Chen, Jiajia Han, Qiyun Lei, Zhipeng Chen, Xiaodong Tang, Wenyu Wu, Shuwen Liu, Xingang Yao
Journal: Acta Pharmaceutica Sinica B (2023)

Extracellular vesicles (EVs) have recently emerged as a promising delivery platform for CRISPR/Cas9 ribonucleoproteins (RNPs), owing to their ability to minimize off-target effects and immune responses. However, enhancements are required to boost the efficiency and safety of Cas9 RNP enrichment within EVs. In response, we employed the Fc/Spa interaction system, in which the human Fc domain was fused to the intracellular domain of PTGFRN-Δ687 and anchored to the EV membrane. Simultaneously, the B domain of the Spa protein was fused to the C domain of cargos such as Cre or spCas9. Due to the robust interaction between Fc and Spa, this method enriched nearly twice the amount of cargo within the EVs. EVs loaded with spCas9 RNP targeting the HSV1 genome exhibited significant inhibition of viral replication in vitro and in vivo. Moreover, following neuron-targeting peptide RVG modification, the in vivo dosage in neural tissues substantially increased, contributing to the clearance of the HSV1 virus in neural tissues and exhibiting a lower off-target efficiency. These findings establish a robust platform for efficient EV-based SpCas9 delivery, offering potential therapeutic advantages for HSV1 infections and other neurological disorders.
Integrating Multi-Omics Data With EHR for Precision Medicine Using Advanced Artificial Intelligence
Authors: Li Tong, Wenqi Shi, Monica Isgut, Yishan Zhong, Peter Lais, Logan Gloster, Jimin Sun, Aniketh Swain, Felipe Giuste, May D. Wang
Journal: IEEE Reviews in Biomedical Engineering (2023)

With the recent advancement of novel biomedical technologies such as high-throughput sequencing and wearable devices, multi-modal biomedical data ranging from multi-omics molecular data to real-time continuous bio-signals are generated at an unprecedented speed and scale every day. For the first time, these multi-modal biomedical data are able to make precision medicine close to a reality. However, due to data volume and the complexity, making good use of these multi-modal biomedical data requires major effort. Researchers and clinicians are actively developing artificial intelligence (AI) approaches for data-driven knowledge discovery and causal inference using a variety of biomedical data modalities. These AI-based approaches have demonstrated promising results in various biomedical and healthcare applications. In this review paper, we summarize the state-of-the-art AI models for integrating multi-omics data and electronic health records (EHRs) for precision medicine. We discuss the challenges and opportunities in integrating multi-omics data with EHRs and future directions. We hope this review can inspire future research and developing in integrating multi-omics data with EHRs for precision medicine.
Diversity in the pathway from medical student to specialist in the Netherlands: a retrospective cohort study
Authors: Lianne Mulder, Anouk Wouters, Eddymurphy U. Akwiwu, Andries S. Koster, Jan Hindrik Ravesloot, Saskia M. Peerdeman, Mahdi Salih, Gerda Croiset, Rashmi A. Kusurkar
Journal: The Lancet Regional Health - Europe (2023)

Medical specialist workforces are not representative of the society they serve, partially due to loss of diversity in the path from student to specialist. We investigated which demographic characteristics of bachelor students of medicine (BSM) are associated with becoming a physician and (particular type of) medical specialist; and whether this suggests 'cloning' (reproduction of sameness) of the existing workforce. We used a retrospective cohort design, based on Statistics Netherlands data of all first-year BSM in 2002–2004 in The Netherlands (N = 4503). We used logistic regression to analyze the impact of sex, migration background, urbanity of residence, parental income and assets categories, and having healthcare professional parents, on being registered as physician or medical specialist in 2021. We compared our results to the national pool of physicians (N = 76,845) and medical specialists (N = 49,956) to identify cloning patterns based on Essed's cultural cloning theory. Female students had higher odds of becoming a physician (OR 1.87 [1.53–2.28], p < 0.001). Physicians with a migration background other than Turkish, Moroccan, Surinamese, Dutch Caribbean or Indonesian (TMSDI) had lower odds of becoming a specialist (OR 0.55 [0.43–0.71], p < 0.001). This was not significant for TMSDI physicians (OR 0.74 [0.54–1.03], p = 0.073). We found a cloning pattern with regard to sex and migration background. Nationwide, physicians with a Turkish or Moroccan migration background, and female physicians with other migration backgrounds, are least likely to be a medical specialist. In light of equity in healthcare systems, we recommend that every recruitment body increases the representativeness of their particular specialist workforce. ODISSEI.
Antenatal corticosteroid treatment and infectious diseases in children: a nationwide observational study
Authors: Katri Räikkönen, Mika Gissler, Eero Kajantie, Terhi Tapiainen
Journal: The Lancet Regional Health - Europe (2023)

Antenatal Corticosteroid Treatment (ACT) improves the outcome of preterm infants, but may influence immune system development and risk of immune-related diseases. We investigated whether ACT is associated with infectious diseases in children born at term (≥37 gestational weeks), and very-to-moderate (<34 gestational weeks), and late (34-36 completed gestational weeks) preterm.
Reprogramming macrophages via immune cell mobilized hydrogel microspheres for osteoarthritis treatments
Authors: Pengcheng Xiao, Xiaoyu Han, Yanran Huang, Jianye Yang, Li Chen, Zhengwei Cai, Ning Hu, Wenguo Cui, Wei Huang
Journal: Bioactive Materials (2023)

Regulating macrophage activation precisely is crucial in treating chronic inflammation in osteoarthritis (OA). However, the stable pro-inflammatory state and deep distribution of macrophages in vivo pose a great challenge to treatment. In this study, inspired by the innate immune, immune cell mobilized hydrogel microspheres were constructed by microfluidic methods and load chemokines, macrophage antibodies and engineered cell membrane vesicles (sEVs) via covalent and non-covalent junctions. The immune cell mobilized hydrogel microspheres, based on a mixture of streptavidin grafted hyaluronic acid methacrylate (HAMA-SA) and Chondroitin sulfate methacrylate (ChSMA) microspheres (HCM), can recruit, capture and reprogram proinflammatory macrophages in the joint cavity to improve the joint inflammatory microenvironment. In vitro experiments demonstrated that immune cell mobilized hydrogel microspheres had excellent macrophage recruitment, capture, and reprogramming abilities. Pro-inflammatory macrophages can be transformed into anti-inflammatory macrophages with an efficiency of 88.5 %. Animal experiments also revealed significant reduction in synovial inflammation and cartilage matrix degradation of OA. Therefore, the immune cell mobilized hydrogel microspheres may be an effective treatment of OA inflammation for the future.
Design and fabrication of customizable microneedles enabled by 3D printing for biomedical applications
Authors: Jia Min Loh, Yun Jie Larissa Lim, Jin Ting Tay, Hui Mei Cheng, Hong Liang Tey, Kun Liang
Journal: Bioactive Materials (2023)

Microneedles (MNs) is an emerging technology that employs needles ranging from 10 to 1000 μm in height, as a minimally invasive technique for various procedures such as therapeutics, disease monitoring and diagnostics. The commonly used method of fabrication, micromolding, has the advantage of scalability, however, micromolding is unable to achieve rapid customizability in dimensions, geometries and architectures, which are the pivotal factors determining the functionality and efficacy of the MNs. 3D printing offers a promising alternative by enabling MN fabrication with high dimensional accuracy required for precise applications, leading to improved performance. Furthermore, enabled by its customizability and one-step process, there is propitious potential for growth for 3D-printed MNs especially in the field of personalized and on-demand medical devices. This review provides an overview of considerations for the key parameters in designing MNs, an introduction on the various 3D-printing techniques for fabricating this new generation of MNs, as well as highlighting the advancements in biomedical applications facilitated by 3D-printed MNs. Lastly, we offer some insights into the future prospects of 3D-printed MNs, specifically its progress towards translation and entry into market.
Consciousness in the cradle: on the emergence of infant experience
Authors: Tim Bayne, Joel Frohlich, Rhodri Cusack, Julia Moser, Lorina Naci
Journal: Trends in Cognitive Sciences (2023)

Although each of us was once a baby, infant consciousness remains mysterious and there is no received view about when, and in what form, consciousness first emerges. Some theorists defend a 'late-onset' view, suggesting that consciousness requires cognitive capacities which are unlikely to be in place before the child's first birthday at the very earliest. Other theorists defend an 'early-onset' account, suggesting that consciousness is likely to be in place at birth (or shortly after) and may even arise during the third trimester. Progress in this field has been difficult, not just because of the challenges associated with procuring the relevant behavioral and neural data, but also because of uncertainty about how best to study consciousness in the absence of the capacity for verbal report or intentional behavior. This review examines both the empirical and methodological progress in this field, arguing that recent research points in favor of early-onset accounts of the emergence of consciousness.
Multifactor artificial intelligence model assists axillary lymph node surgery in breast cancer after neoadjuvant chemotherapy: multicenter retrospective cohort study
Authors: Teng Zhu, Yu-Hong Huang, Wei Li, Yi-Min Zhang, Ying-Yi Lin, Min-Yi Cheng, Zhi-Yong Wu, Guo-Lin Ye, Ying Lin, Kun Wang
Journal: International Journal of Surgery (2023)

Background: The high false negative rate associated with sentinel lymph node biopsy (SLNB) often leads to unnecessary axillary lymph node dissection (ALND) following neoadjuvant chemotherapy (NAC) in breast cancer. We aimed to develop a multi-factor artificial intelligence (AI) model to aid in axillary lymph node surgery. Materials and Methods: A total of 1038 patients were enrolled, comprising 234 patients in the primary cohort, 723 patients in three external validation cohorts, and 81 patients in the prospective cohort. For predicting axillary lymph node response to NAC, robust longitudinal radiomics features were extracted from pre-NAC and post-NAC magnetic resonance images. The U test, the least absolute shrinkage and selection operator, and the spearman analysis were used to select the most significant features. A machine learning stacking model was constructed to detect ALN metastasis after NAC. By integrating the significant predictors, we developed a multi-factor AI-assisted surgery pipeline and compared its performance and false negative rate (FNR) with that of SLNB alone. Results: The machine learning stacking model achieved excellent performance in detecting ALN metastasis, with an area under the curve (AUC) of 0.958 in the primary cohort, 0.881 in the external validation cohorts, and 0.882 in the prospective cohort. Furthermore, the introduction of AI-assisted surgery reduced the FNRs from 14.88% (18/121) to 4.13% (5/121) in the primary cohort, from 16.55% (49/296) to 4.05% (12/296) in the external validation cohorts, and from 13.64% (3/22) to 4.55% (1/22) in the prospective cohort. Notably, when more than two SLNs were removed, the FNRs further decreased to 2.78% (2/72) in the primary cohort, 2.38% (4/168) in the external validation cohorts, and 0% (0/15) in the prospective cohort. Conclusion: Our study highlights the potential of AI-assisted surgery as a valuable tool for evaluating ALN response to NAC, leading to a reduction in unnecessary ALND procedures.
The Two Front War on Reproductive Rights—When the Right to Abortion is Banned, Can the Right to Refuse Obstetrical Interventions Be Far behind?
Authors: Howard Minkoff, Raaga Unmesha Vullikanti, Mary Faith Marshall
Journal: The American Journal of Bioethics (2023)

AbstractThe loss of the federally protected constitutional right to an abortion is a threat to the already tenuous autonomy of pregnant people, and may augur future challenges to their right to refuse unwanted obstetric interventions. Even before Roe's demise, pregnancy led to constraints on autonomy evidenced by clinician-led legal incursions against patients who refused obstetric interventions. In Dobbs v. Jackson Women's Health Organization, the Supreme Court found that the right to liberty espoused in the Constitution does not extend to a pregnant person's right to an abortion. With Roe's demise, the right to request specific types of care has been vitiated. The same argument underpinning that holding may now become ballast for attacks on the traditionally more robust right, the right to refuse. Here we discuss how the elevation of fetal and embryonic rights may lead to a cascade of medical intrusions and deprivations of liberty against pregnant persons, and offer an argument opposing these improprieties.Keywords: AbortionDobbsfetuspersonrefuserights DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Notes1 Based in common law and the Constitutional precepts of an individual's right to bodily integrity, self-determination, and privacy.2 Justice Cardozo labeled the offending surgeons as "ministers of healing [who] have proved unfaithful to their trust."3 Sims experimented on Ms. Westcott 29 times in pursuit of a definitive surgical approach to vesico-vaginal fistula.4 Trials were held in the Star Chamber (an English court late 15th to mid-17th centuries) to ensure fair enforcement of laws against those deemed too politically or socially powerful to try in common law courts. It was abolished in 1642 after eventual abuse of its powers, including torture to obtain confessions and punishment of jurors who found against the Crown. Today it is a pejorative term denoting a closed or secret administrative or court proceeding resulting in an arbitrary finding or violation of due process.5 A similar argument has been posited by Judith Jarvis Thomson in her classic violinist analogy.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Charged Fibrous Dressing to Promote Diabetic Chronic Wound Healing
Authors: Xiaomeng Yang, Wei Li, Youmei Liu, Ni Cao, Yang He, Qiangqiang Sun, Shaobing Zhou
Journal: Advanced Healthcare Materials (2023)

Diabetic chronic wounds cause a significant amount of pain to patients because of their low cure rates and high recurrence rates. Traditional approaches to treating diabetic chronic wounds often involve the delivery of drugs or cytokines that regulate the microenvironment and eliminate bacterial infection in the wound area, but they are passive in controlling cell behaviors and may lead to drug resistance. Emerging drug-free wound treatments are important for convenient, effective, and safe treatment strategies. However, the current approaches cannot fully promote tissue regeneration or prevent bacterial infections. Here, the efficacy of a negatively charged fiber dressing in promoting diabetic chronic wound healing is investigated. The negatively charged fiber dressing can generate reactive oxygen species to inhibit bacterial reproduction with the assistance of ultrasound during the inflammatory phase. Furthermore, the dressing provides an electrostatic field that regulates cellular behavior during the inflammatory and proliferative phases. In particular, the dressing can promote fibroblast migration and induce macrophage polarization and neovascularization without any additional drugs. It is demonstrated that this strategy enables the healing of diabetic chronic wounds in a mouse model, achieving effective wound closure over a 12-day treatment cycle and providing a drug-free therapeutic strategy for diabetic chronic wound care.